STAT3 is a promising anticancer drug target.Its activation involves dimerization via intermolecular pTyr-SH2 interaction[1].Thus,blocking this interaction is a feasible approach to inhibit STAT3 activation for the design of a new class of anticancer drugs.In this study,nearly 204,000 compounds screened by virtual screening,samples of top 100 compounds identified as candidate small-molecule inhibitors of Stat3 are evaluated by Stat3-dependent luciferase reporter as well as cell-based assays.Compound 55 is identified as the best match.Further investigation demonstrated that compound 55 may bind to a different site on the surface of SH2 domain.Moreover,a series of 6-aminobenzo[d]thiazole-2-thiol derivatives have been designed and synthesized,and their biological activities are also evaluated.Compound 2-16 inhibited the IL-6/STAT3 pathway with an IC50 value of 1.16 μM and is a promising lead compound for further design and optimization.